Circumcision, HPV, and HIV

After a period of relative quiet, I found two interesting new studies in my PubMed alert this morning.

First, Wawer et al. published Effect of circumcision of HIV-negative men on transmission of human papillomavirus to HIV-negative women: a randomised trial in Rakai, Uganda. This is a fascinating study, not least because it is yet another study cleverly piggy-backed on one of the randomised controlled trials that effectively proved that circumcision reduces the risk of HIV. Results have been published previously showing that circumcision reduced the risk of (and increased clearance of) HPV infection in men; what's unusual about this study is that it directly measured the effect on infection in women (to be precise, the female partners of the men in the trial). And as previous observational studies indicated, the risk was reduced, from 38.7% to 27.8%.

The significance of this, of course, is that HPV is the virus responsible for cervical cancer in women (and about half of penile cancers in men). According to the World Health Organisation, cervical cancer is the second biggest cause of cancer deaths worldwide, resulting in 288,000 deaths annually. Could circumcision programmes reduce those deaths by a third, as a happy side-effect of HIV prevention programmes?

It does raise an interesting ethical question, though: when weighing costs and benefits of circumcision, how much weight should be given to something that does not affect the male directly, but rather a possible partner in the future? It's a difficult question, and I don't claim to have the answers.

Moving on, Anderson et al. have published what looks to be an interesting review entitled HIV Infection and Immune Defense of the Penis. Their subject matter, of course, is the mechanism by which circumcision protects against HIV. I haven't had the opportunity to read the full text, but from the abstract it appears that they reject the traditional view of the foreskin's mucosal layer as an HIV target, instead preferring a model in which the subpreputial cavity traps HIV and HIV-infected cells, bringing them into contact with the urethra. It's an interesting hypothesis, but I personally suspect that attempts to find a single explanation are doomed to failure; I believe that the protective effect seen is a result of multiple mechanisms acting together.